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[PMID]:29232606
[Au] Autor:Kotnala A; Senthilkumari S; Halder N; Kumar A; Velpandian T
[Ad] Endereço:Ocular Pharmacology & Pharmacy Division, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
[Ti] Título:Microwave assisted synthesis for A2E and development of LC-ESI-MS method for quantification of ocular bisretinoids in human retina.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1073:10-18, 2018 Jan 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To develop a microwave assisted method for the rapid synthesis of A2E and also to develop a method to quantify N-retinylidene-N-retinylethanolamine(A2E), all-trans retinal dimer (ATRD), A2-glycerophospho ethanolamine (A2GPE), dihydropyridine phosphatidyl ethanolamine (A2DHPE) and monofuran A2E (MFA2E) in age matched retina. METHODS: The development of microwave assisted synthesis of A2E, its purification and characterization for its utility in quantification in human retina. The semi-quantitative method development using LC-ESI-MS, LC-ESI-MS/MS and LC-APCI-MS/MS from pooled macula and peripheral retina for the bisretinoid analysis has been done. RESULTS: Maximum A2E conversion using microwave assisted process took place at 80°C for 45min with a yield of 55.01%. Highly sensitive and specific mass spectrometric method was developed using reverse phase C-18 separation with positive electrospray ionization and positive atmospheric phase chemical ionization of tandom mass spectrometry. A gradient mobile phase separation was achieved using water and methanol with 0.1% TFA. Multiple reaction monitoring acquisition for ESI and APCI was performed at ATRD m/z 551.2/522.2, A2GPE m/z 746.4/729.5, A2DHPEm/z 594.4/576.5, MFA2E m/z 608.2/591.2, A2E m/z 592.4/418.2. Method was validated using LC-ESI-SIM mode to determine selectivity, linearity, sensitivity, precision and accuracy. CONCLUSION: An attempt towards optimization of the synthetic procedure of A2E was made so as to reduce the lengthy reaction time without compromising the yield. Developed method was capable enough for the detection of low level of bisretinids in retina.
[Mh] Termos MeSH primário: Cromatografia Líquida/métodos
Micro-Ondas
Retina/química
Retinoides/análise
Retinoides/síntese química
Espectrometria de Massas por Ionização por Electrospray/métodos
[Mh] Termos MeSH secundário: Adulto
Idoso
Seres Humanos
Masculino
Meia-Idade
Retinoides/química
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (A2-E (N-retinylidene-N-retinylethanolamine)); 0 (Retinoids)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE


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[PMID]:28465464
[Au] Autor:Sun Y; Lin Z; Liu CH; Gong Y; Liegl R; Fredrick TW; Meng SS; Burnim SB; Wang Z; Akula JD; Pu WT; Chen J; Smith LEH
[Ad] Endereço:Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, Boston, MA 02115.
[Ti] Título:Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos.
[So] Source:J Exp Med;214(6):1753-1767, 2017 Jun 05.
[Is] ISSN:1540-9538
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pathological neovessels growing into the normally avascular photoreceptors cause vision loss in many eye diseases, such as age-related macular degeneration and macular telangiectasia. Ocular neovascularization is strongly associated with inflammation, but the source of inflammatory signals and the mechanisms by which these signals regulate the disruption of avascular privilege in photoreceptors are unknown. In this study, we found that c-Fos, a master inflammatory regulator, was increased in photoreceptors in a model of pathological blood vessels invading photoreceptors: the very low-density lipoprotein receptor-deficient ( ) mouse. Increased c-Fos induced inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor (TNF), leading to activation of signal transducer and activator of transcription 3 (STAT3) and increased TNFα-induced protein 3 (TNFAIP3) in photoreceptors. IL-6 activated the STAT3/vascular endothelial growth factor A (VEGFA) pathway directly, and elevated TNFAIP3 suppressed SOCS3 (suppressor of cytokine signaling 3)-activated STAT3/VEGFA indirectly. Inhibition of c-Fos using photoreceptor-specific (adeno-associated virus)- (human rhodopsin kinase)- or a chemical inhibitor substantially reduced the pathological neovascularization and rescued visual function in mice. These findings suggested that the photoreceptor c-Fos controls blood vessel growth into the normally avascular photoreceptor layer through the inflammatory signal-induced STAT3/VEGFA pathway.
[Mh] Termos MeSH primário: Inflamação/metabolismo
Inflamação/patologia
Células Fotorreceptoras de Vertebrados/metabolismo
Proteínas Proto-Oncogênicas c-fos/metabolismo
Neovascularização Retiniana/metabolismo
Neovascularização Retiniana/patologia
Transdução de Sinais
[Mh] Termos MeSH secundário: Animais
Dependovirus/metabolismo
Interleucina-6/metabolismo
Camundongos
Neurônios/efeitos dos fármacos
Neurônios/metabolismo
Células Fotorreceptoras de Vertebrados/efeitos dos fármacos
Células Fotorreceptoras de Vertebrados/patologia
RNA Interferente Pequeno/metabolismo
Receptores de LDL/deficiência
Receptores de LDL/metabolismo
Retina/efeitos dos fármacos
Retina/patologia
Retina/fisiopatologia
Retinoides/farmacologia
Fator de Transcrição STAT3/metabolismo
Transdução de Sinais/efeitos dos fármacos
Fator A de Crescimento do Endotélio Vascular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-6); 0 (Proto-Oncogene Proteins c-fos); 0 (RNA, Small Interfering); 0 (Receptors, LDL); 0 (Retinoids); 0 (SR 11302); 0 (STAT3 Transcription Factor); 0 (VLDL receptor); 0 (Vascular Endothelial Growth Factor A)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180117
[Lr] Data última revisão:
180117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1084/jem.20161645


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[PMID]:29053764
[Au] Autor:Nakajima E; Hammond KB; Hirata M; Shearer TR; Azuma M
[Ad] Endereço:Senju Laboratory of Ocular Sciences, Senju Pharmaceutical Corporation Limited, Portland, Oregon, United States.
[Ti] Título:Contribution of Calpain and Caspases to Cell Death in Cultured Monkey RPE Cells.
[So] Source:Invest Ophthalmol Vis Sci;58(12):5412-5420, 2017 Oct 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: AMD is the leading cause of human vision loss after 65 years of age. Several mechanisms have been proposed: (1) age-related failure of the choroidal vasculature leads to loss of RPE; (2) RPE dysfunctions due to accumulation of phagocytized, but unreleased A2E (N-retinylidene-N-retinylethanolamine); (3) zinc deficiency activation of calpain and caspase proteases, leading to cell death. The purpose of the present study is to compare activation of calpain and caspase in monkey RPE cells cultured under hypoxia or with A2E. Methods: Monkey primary RPE cells were cultured under hypoxic conditions in a Gaspak pouch or cultured with synthetic A2E. Immunoblotting was used to detect activation of calpain and caspase. Calpain inhibitor, SNJ-1945, and pan-caspase inhibitor, z-VAD-fmk, were used to confirm activation of the proteases. Results: (1) Hypoxia and A2E each decreased viability of RPE cells in a time-dependent manner. (2) Incubation under hypoxia alone induced activation of calpain, but not caspases. SNJ-1945 inhibited calpain activation, but z-VAD-fmk did not. (3) Incubation with A2E alone induced activation of calpain, caspase-9, and caspase-3. SNJ-1945 inhibited calpain activation. z-VAD-fmk inhibited caspase activation, suggesting no interaction between calpain and caspases. Conclusions: Hypoxia activated the calpain pathway, while A2E activated both calpain and caspase pathways in monkey RPE cells. Such knowledge may be utilized in the treatment of AMD if inhibitor drugs against calpain and/or caspase are used to prevent RPE dysfunction caused by hypoxia or A2E.
[Mh] Termos MeSH primário: Apoptose/fisiologia
Calpaína/metabolismo
Caspases/metabolismo
Epitélio Pigmentado da Retina/metabolismo
[Mh] Termos MeSH secundário: Animais
Calpaína/antagonistas & inibidores
Inibidores de Caspase/farmacologia
Hipóxia Celular/fisiologia
Sobrevivência Celular
Células Cultivadas
Inibidores Enzimáticos/farmacologia
Immunoblotting
Macaca mulatta
Microscopia de Contraste de Fase
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Epitélio Pigmentado da Retina/efeitos dos fármacos
Epitélio Pigmentado da Retina/patologia
Retinoides/farmacologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (A2-E (N-retinylidene-N-retinylethanolamine)); 0 (Caspase Inhibitors); 0 (Enzyme Inhibitors); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Retinoids); EC 3.4.22.- (Calpain); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171021
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-22325


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[PMID]:28813718
[Au] Autor:Du M; Phelps E; Balangue MJ; Dockins A; Moiseyev G; Shin Y; Kane S; Otalora L; Ma JX; Farjo R; Farjo KM
[Ad] Endereço:Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
[Ti] Título:Transgenic Mice Over-Expressing RBP4 Have RBP4-Dependent and Light-Independent Retinal Degeneration.
[So] Source:Invest Ophthalmol Vis Sci;58(10):4375­4383, 2017 08 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: Transgenic mice overexpressing serum retinol-binding protein (RBP4-Tg) develop progressive retinal degeneration, characterized by microglia activation, yet the precise mechanisms underlying retinal degeneration are unclear. Previous studies showed RBP4-Tg mice have normal ocular retinoid levels, suggesting that degeneration is independent of the retinoid visual cycle or light exposure. The present study addresses whether retinal degeneration is light-dependent and RBP4-dependent by testing the effects of dark-rearing and pharmacological lowering of serum RBP4 levels, respectively. Methods: RBP4-Tg mice reared on normal mouse chow in normal cyclic light conditions were directly compared to RBP4-Tg mice exposed to chow supplemented with the RBP4-lowering compound A1120 or dark-rearing conditions. Quantitative retinal histological analysis was conducted to assess retinal degeneration, and electroretinography (ERG) and optokinetic tracking (OKT) tests were performed to assess retinal and visual function. Ocular retinoids and bis-retinoid A2E were quantified. Results: Dark-rearing RBP4-Tg mice effectively reduced ocular bis-retinoid A2E levels, but had no significant effect on retinal degeneration or dysfunction in RBP4-Tg mice, demonstrating that retinal degeneration is light-independent. A1120 treatment lowered serum RBP4 levels similar to wild-type mice, and prevented structural retinal degeneration. However, A1120 treatment did not prevent retinal dysfunction in RBP4-Tg mice. Moreover, RBP4-Tg mice on A1120 diet had significant worsening of OKT response and loss of cone photoreceptors compared to RBP4-Tg mice on normal chow. This may be related to the very significant reduction in retinyl ester levels in the retina of mice on A1120-supplemented diet. Conclusions: Retinal degeneration in RBP4-Tg mice is RBP4-dependent and light-independent.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/fisiologia
Lesões Experimentais por Radiação/genética
Retina/efeitos da radiação
Degeneração Retiniana/genética
Proteínas Plasmáticas de Ligação ao Retinol/genética
[Mh] Termos MeSH secundário: Animais
Adaptação à Escuridão
Eletrorretinografia
Feminino
Luz
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Piperidinas/farmacologia
Lesões Experimentais por Radiação/metabolismo
Lesões Experimentais por Radiação/patologia
Degeneração Retiniana/metabolismo
Degeneração Retiniana/patologia
Retinoides/metabolismo
Proteínas Plasmáticas de Ligação ao Retinol/antagonistas & inibidores
Proteínas Plasmáticas de Ligação ao Retinol/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (A1120 agent); 0 (Piperidines); 0 (Rbp4 protein, mouse); 0 (Retinoids); 0 (Retinol-Binding Proteins, Plasma)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170817
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-22107


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[PMID]:28758396
[Au] Autor:Chelstowska S; Widjaja-Adhi MAK; Silvaroli JA; Golczak M
[Ad] Endereço:Laboratory of Hematology and Flow Cytometry, Department of Hematology, Military Institute of Medicine , Warsaw 04141, Poland.
[Ti] Título:Impact of LCA-Associated E14L LRAT Mutation on Protein Stability and Retinoid Homeostasis.
[So] Source:Biochemistry;56(34):4489-4499, 2017 Aug 29.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Vitamin A (all-trans-retinol) is metabolized to the visual chromophore (11-cis-retinal) in the eyes and to all-trans-retinoic acid, a hormone like compound, in most tissues. A key enzyme in retinoid metabolism is lecithin:retinol acyltransferase (LRAT), which catalyzes the esterification of vitamin A. The importance of LRAT is indicated by pathogenic missense and nonsense mutations, which cause devastating blinding diseases. Retinoid-based chromophore replacement therapy has been proposed as treatment for these types of blindness based on studies in LRAT null mice. Here, we analyzed the structural and biochemical basis for retinal pathology caused by mutations in the human LRAT gene. Most LRAT missense mutations associated with retinal degeneration are localized within the catalytic domain, whereas E14L substitution is localized in an N-terminal α-helix, which has been implicated in interaction with the phospholipid bilayer. To elucidate the biochemical consequences of this mutation, we determined LRAT(E14L)'s enzymatic properties, protein stability, and impact on ocular retinoid metabolism. Bicistronic expression of LRAT(E14L) and enhanced green fluorescence protein revealed instability and accelerated proteosomal degradation of this mutant isoform. Surprisingly, instability of LRAT(E14L) did not abrogate the production of the visual chromophore in a cell-based assay. Instead, expression of LRAT(E14L) led to a rapid increase in cellular levels of retinoic acid upon retinoid supplementation. Thus, our study unveils the potential role of retinoic acid in the pathology of a degenerative retinal disease with important implications for the use of retinoid-based therapeutics in affected patients.
[Mh] Termos MeSH primário: Aciltransferases/metabolismo
Homeostase
Mutação de Sentido Incorreto
Degeneração Retiniana/enzimologia
Retinoides/metabolismo
[Mh] Termos MeSH secundário: Aciltransferases/química
Aciltransferases/genética
Substituição de Aminoácidos
Animais
Estabilidade Enzimática
Seres Humanos
Camundongos
Células NIH 3T3
Estrutura Secundária de Proteína
Degeneração Retiniana/genética
Degeneração Retiniana/patologia
Retinoides/química
Retinoides/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Retinoids); EC 2.3.- (Acyltransferases); EC 2.3.1.- (lecithin-retinol acyltransferase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171115
[Lr] Data última revisão:
171115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00451


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[PMID]:28672005
[Au] Autor:Cubizolle A; Guillou L; Mollereau B; Hamel CP; Brabet P
[Ad] Endereço:Inserm U1051, Institute for Neurosciences of Montpellier, Montpellier, France.
[Ti] Título:Fatty acid transport protein 1 regulates retinoid metabolism and photoreceptor development in mouse retina.
[So] Source:PLoS One;12(7):e0180148, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In retinal pigment epithelium (RPE), RPE65 catalyzes the isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol in the visual cycle and controls the rhodopsin regeneration rate. However, the mechanisms by which these processes are regulated are still unclear. Fatty Acid Transport Protein 1 (FATP1) is involved in fatty acid uptake and lipid metabolism in a variety of cell types. FATP1 co-localizes with RPE65 in RPE and inhibits its isomerase activity in vitro. Here, we further investigated the role of FATP1 in the visual cycle using transgenic mice that overexpress human FATP1 specifically in the RPE (hFATP1TG mice). The mice displayed no delay in the kinetics of regeneration of the visual chromophore 11-cis-retinal after photobleaching and had no defects in light sensitivity. However, the total retinoid content was higher in the hFATP1TG mice than in wild type mice, and the transgenic mice also displayed an age-related accumulation (up to 40%) of all-trans-retinal and retinyl esters that was not observed in control mice. Consistent with these results, hFATP1TG mice were more susceptible to light-induced photoreceptor degeneration. hFATP1 overexpression also induced an ~3.5-fold increase in retinosome autofluorescence, as measured by two-photon microscopy. Interestingly, hFATP1TG retina contained ~25% more photoreceptor cells and ~35% longer outer segments than wild type mice, revealing a non-cell-autonomous effect of hFATP1 expressed in the RPE. These data are the first to show that FATP1-mediated fatty acid uptake in the RPE controls both retinoid metabolism in the outer retina and photoreceptor development.
[Mh] Termos MeSH primário: Proteínas de Transporte de Ácido Graxo/fisiologia
Células Fotorreceptoras de Vertebrados/metabolismo
Retina/metabolismo
Retinoides/metabolismo
[Mh] Termos MeSH secundário: Animais
Eletrorretinografia
Seres Humanos
Camundongos
Visão Ocular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fatty Acid Transport Proteins); 0 (Retinoids); 0 (Slc27a1 protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170704
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180148


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[PMID]:28657366
[Au] Autor:Le Moigne M; Bulteau S; Grall-Bronnec M; Gerardin M; Fournier JP; Jonville-Bera AP; Jolliet P; Dreno B; Victorri-Vigneau C
[Ad] Endereço:a Dermato-Oncology Unit , University Hospital Hôtel-Dieu , Nantes , France.
[Ti] Título:Psychiatric disorders, acne and systemic retinoids: comparison of risks.
[So] Source:Expert Opin Drug Saf;16(9):989-995, 2017 Sep.
[Is] ISSN:1744-764X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The link between isotretinoin, treatment of a severe form of acne, and psychiatric disorders remains controversial, as acne itself could explain the occurrence of psychiatric disorders. This study aims at assessing the disproportionality of psychiatric adverse events reported with isotretinoin in the French National PharmacoVigilance Database, compared with other systemic acne treatments and systemic retinoids. MATERIALS AND METHODS: Data were extracted from the French National PharmacoVigilance Database for systemic acne treatments, systemic retinoids and drugs used as comparators. Each report was subjected to double-blind analysis by two psychiatric experts. A disproportionality analysis was performed, calculating the number of psychiatric ADRs divided by the total number of notifications for each drug of interest. RESULTS: Concerning acne systemic treatments: all 71 reports of severe psychiatric disorders involved isotretinoin, the highest proportion of mild/moderate psychiatric adverse events was reported with isotretinoin (14.1%). Among systemic retinoids, the highest proportion of severe and mild/moderate psychiatric events occurred with isotretinoin and alitretinoin. CONCLUSION: Our study raises the hypothesis that psychiatric disorders associated with isotretinoin are related to a class effect of retinoids, as a signal emerges for alitretinoin. Complementary studies are necessary to estimate the risk and further determine at-risk populations.
[Mh] Termos MeSH primário: Acne Vulgar/tratamento farmacológico
Fármacos Dermatológicos/uso terapêutico
Transtornos Mentais/induzido quimicamente
Retinoides/uso terapêutico
[Mh] Termos MeSH secundário: Sistemas de Notificação de Reações Adversas a Medicamentos
Bases de Dados Factuais
Fármacos Dermatológicos/efeitos adversos
Feminino
França
Seres Humanos
Isotretinoína/efeitos adversos
Isotretinoína/uso terapêutico
Masculino
Transtornos Mentais/epidemiologia
Farmacovigilância
Retinoides/efeitos adversos
Risco
Índice de Gravidade de Doença
Tretinoína/efeitos adversos
Tretinoína/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dermatologic Agents); 0 (Retinoids); 1UA8E65KDZ (alitretinoin); 5688UTC01R (Tretinoin); EH28UP18IF (Isotretinoin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170629
[St] Status:MEDLINE
[do] DOI:10.1080/14740338.2017.1344641


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[PMID]:28651825
[Au] Autor:Zhang M; Silverberg JI; Kaffenberger BH
[Ad] Endereço:Department of Internal Medicine, Division of Dermatology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
[Ti] Título:Prescription patterns and costs of acne/rosacea medications in Medicare patients vary by prescriber specialty.
[So] Source:J Am Acad Dermatol;77(3):448-455.e2, 2017 Sep.
[Is] ISSN:1097-6787
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Prescription patterns for acne/rosacea medications have not been described in the Medicare population, and comparisons across specialties are lacking. OBJECTIVE: To describe the medications used for treating acne/rosacea in the Medicare population and evaluate differences in costs between specialties. METHODS: A cross-sectional study was performed of the 2008 and 2010 Centers for Medicare and Medicaid Services Prescription Drug Profiles, which contains 100% of Medicare part D claims. RESULTS: Topical antibiotics accounted for 63% of all prescriptions. Patients ≥65 years utilized more oral tetracycline-class antibiotics and less topical retinoids. Specialists prescribed brand name drugs for the most common topical retinoids and most common topical antibiotics more frequently than family medicine/internal medicine (FM/IM) physicians by 6%-7%. Topical retinoids prescribed by specialists were, on average, $18-$20 more in total cost and $2-$3 more in patient cost than the same types of prescriptions from FM/IM physicians per 30-day supply. Specialists (60%) and IM physicians (56%) prescribed over twice the rate of branded doxycycline than FM doctors did (27%). The total and patient costs for tetracycline-class antibiotics were higher from specialists ($18 and $4 more, respectively) and IM physicians ($3 and $1 more, respectively) than they were from FM physicians. LIMITATIONS: The data might contain rare prescriptions used for conditions other than acne/rosacea, and suppression algorithms might underestimate the number of specialist brand name prescriptions. CONCLUSION: Costs of prescriptions for acne/rosacea from specialists are higher than those from primary care physicians and could be reduced by choosing generic and less expensive options.
[Mh] Termos MeSH primário: Acne Vulgar/tratamento farmacológico
Antibacterianos/economia
Antibacterianos/uso terapêutico
Custos de Medicamentos
Padrões de Prática Médica
Retinoides/economia
Retinoides/uso terapêutico
Rosácea/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Estudos Transversais
Prescrições de Medicamentos/economia
Prescrições de Medicamentos/estatística & dados numéricos
Feminino
Seres Humanos
Masculino
Medicare
Medicina
Meia-Idade
Estados Unidos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Retinoids)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170628
[St] Status:MEDLINE


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[PMID]:28642153
[Au] Autor:Miro Estruch I; Melchers D; Houtman R; de Haan LHJ; Groten JP; Louisse J; Rietjens IMCM
[Ad] Endereço:Division of Toxicology, Wageningen University, Stippeneng 4, 6708 WE Wageningen, The Netherlands. Electronic address: ignacio.miroestruch@wur.nl.
[Ti] Título:Characterization of the differential coregulator binding signatures of the Retinoic Acid Receptor subtypes upon (ant)agonist action.
[So] Source:Biochim Biophys Acta;1865(9):1195-1206, 2017 09.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Retinoic Acid Receptor alpha (RARα/NR1B1), Retinoic Acid Receptor beta (RARß/NR1B2) and Retinoic Acid Receptor gamma (RARγ/NR1B3) are transcription factors regulating gene expression in response to retinoids. Within the RAR genomic pathways, binding of RARs to coregulators is a key intermediate regulatory phase. However, ligand-dependent interactions between the wide variety of coregulators that may be present in a cell and the different RAR subtypes are largely unknown. The aim of this study is to characterize the coregulator binding profiles of RARs in the presence of the pan-agonist all-trans-Retinoic Acid (AtRA); the subtype-selective agonists Am80 (RARα), CD2314 (RARß) and BMS961 (RARγ); and the antagonist Ro415253. To this end, we used a microarray assay for coregulator-nuclear receptor interactions to assess RAR binding to 154 motifs belonging to >60 coregulators. The results revealed a high number of ligand-dependent RAR-coregulator interactions among all RAR variants, including many binding events not yet described in literature. Next, this work confirmed a greater ligand-independent activity of RARß compared to the other RAR subtypes based on both higher basal and lower ligand-driven coregulator binding. Further, several coregulator motifs showed selective binding to a specific RAR subtype. Next, this work showed that subtype-selective agonists can be successfully discriminated by using coregulator binding assays. Finally this study demonstrated the possible applications of a coregulator binding assay as a tool to discriminate between agonistic/antagonistic actions of ligands. The RAR-coregulator interactions found will be of use to direct further studies to better understand the mechanisms driving the eventual actions of retinoids.
[Mh] Termos MeSH primário: Receptores do Ácido Retinoico/química
Receptor alfa de Ácido Retinoico/química
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Antracenos/farmacologia
Benzoatos/farmacologia
Sítios de Ligação
Análise Serial de Proteínas
Ligação Proteica
Domínios Proteicos
Receptores do Ácido Retinoico/agonistas
Receptores do Ácido Retinoico/antagonistas & inibidores
Proteínas Recombinantes/metabolismo
Elementos de Resposta
Receptor alfa de Ácido Retinoico/agonistas
Receptor alfa de Ácido Retinoico/antagonistas & inibidores
Retinoides/farmacologia
Relação Estrutura-Atividade
Tetra-Hidronaftalenos/farmacologia
Tiofenos/farmacologia
Tretinoína/farmacologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anthracenes); 0 (BMS 961); 0 (Benzoates); 0 (CD2314); 0 (Receptors, Retinoic Acid); 0 (Recombinant Proteins); 0 (Retinoic Acid Receptor alpha); 0 (Retinoids); 0 (Ro 415253); 0 (Tetrahydronaphthalenes); 0 (Thiophenes); 0 (retinoic acid receptor beta); 0 (retinoic acid receptor gamma); 08V52GZ3H9 (tamibarotene); 5688UTC01R (Tretinoin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE


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[PMID]:28631680
[Au] Autor:Semenov FV; Leonov GK
[Ad] Endereço:Kuban State Medical University, Ministry of Health of the Russian Federation, Krasnodar, 350063.
[Ti] Título:[The influence of retinoids on the regeneration of an open osteal wound].
[Ti] Título:Vliianie retinoidov na regeneratsiiu otkrytoi kostnoi rany..
[So] Source:Vestn Otorinolaringol;82(3):42-44, 2017.
[Is] ISSN:0042-4668
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:The objective of the present study was to elucidate the influence of retinoid-based pharmaceutical products on the process of regeneration of the tissues surrounding an open osteal wound under the experimental conditions. The experiments were carried out using 20 'Sovetskaya shinshilla' rabbits (12 males and 8 females). The animals with the modelled open osteal wound underwent daily treatment by the placement of the dressings impregnated with a mixture of dioxo-methyltetrahydropyrimidine and chloramphenicol ointments supplemented by 0.05% retinoic acid (1:1:1). The rabbits of the control group were treated using the dressings impregnated only with a mixture of dioxo-methyltetrahydropyrimidine and chloramphenicol ointments containing no retinoic acid. The study has demonstrated that the application of the retinoid-based medications for the treatment of the open osteal wound resulted in the well apparent positive dynamics of the wound process in comparison with that in the control animals. It is concluded that the data obtained give evidence that retinoid-based preparations can be used as an adjuvant treatment for the acceleration and promotion of the wound healing process in the trepanation cavity following sanation surgery on the middle ear.
[Mh] Termos MeSH primário: Regeneração Óssea/efeitos dos fármacos
Osso e Ossos
Cloranfenicol/farmacologia
Retinoides/farmacologia
Ferida Cirúrgica
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos/farmacologia
Animais
Antibacterianos/farmacologia
Antioxidantes/farmacologia
Bandagens
Osso e Ossos/efeitos dos fármacos
Osso e Ossos/lesões
Osso e Ossos/fisiopatologia
Combinação de Medicamentos
Feminino
Masculino
Coelhos
Ferida Cirúrgica/diagnóstico
Ferida Cirúrgica/fisiopatologia
Ferida Cirúrgica/terapia
Resultado do Tratamento
Cicatrização/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Anti-Bacterial Agents); 0 (Antioxidants); 0 (Drug Combinations); 0 (Retinoids); 66974FR9Q1 (Chloramphenicol)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170621
[St] Status:MEDLINE
[do] DOI:10.17116/otorino201782342-44



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